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Digital archive of theses discussed at the University of Pisa

 

Thesis etd-11022023-161839


Thesis type
Tesi di specializzazione (4 anni)
Author
FRANCONI, IACOPO
URN
etd-11022023-161839
Thesis title
Beyond Minimum Inhibitory Concentration in yeasts: Fungicidal activity of Amphotericin B against azole-resistant Candida parapsilosis.
Department
RICERCA TRASLAZIONALE E DELLE NUOVE TECNOLOGIE IN MEDICINA E CHIRURGIA
Course of study
MICROBIOLOGIA E VIROLOGIA
Supervisors
relatore Prof.ssa Lupetti, Antonella
Keywords
  • Candida parapsilosis
  • azole-resistance
  • minimum fungicidal concentration
  • fungicidal tests
  • amphotericin B
  • antifungal resistance
Graduation session start date
24/11/2023
Availability
Withheld
Release date
24/11/2093
Summary
Antimicrobial resistance is a matter of raising concern especially in fungal diseases. Multiple reports all over the world are highlighting a worrisome increase in azole- and echinocandin-resistance among fungal pathogens especially in Candida species, as reported in the recently published fungal pathogens priority list made by the WHO. Despite continuous efforts and advances in infection control, development of new antifungal molecules and research on molecular mechanisms of antifungal resistance made by the scientific community, trends in invasive fungal diseases and associated antifungal resistance are on the rise, hindering therapeutic options and clinical cure. Since the last decade numerous studies reported clinical outbreaks of azole non-susceptible Candida parapsilosis. Echinocandins are the recommended empiric therapy and the first line treatment for azole non-susceptible Candida spp. blood stream infections. However, echinocandins exert only a fungistatic effect on C. parapsilosis and increased tolerance to these compounds has been associated with persistent candidemia. Only Amphotericin B showed a fungicidal effect on C. parapsilosis, still data on its fungicidal activity on azole-resistant isolates and correlation with MIC values and clinical outcomes are scarce. Aim of this study was to evaluate fungicidal effect of Amphotericin B with Minimum Fungicidal Concentration method and its correlation with Minimum Inhibitory Concentration values on azole-resistant C. parapsilosis isolated from clinical samples. Amphotericin B fungicidal activity was evaluated on 11 clinical isolates and 1 reference strain. Median MFC value was 2 µg/mL (range 0.5-4 µg/mL). Median MFC/MIC ratio was 2-4 found in 6 out of 12 isolates (50%) tested. Lowest MFC/MIC ratio reported was 1. Spearman’s correlation test was run to evaluate the relationship between MIC and MFC values. A statistically significant strong association was found between the two variables (rs = 0.783, p < 0.001). This study confirms Amphotericin B as a potential and resourceful antifungal therapy in the context of rising antifungal resistance, especially in the case of azole-resistant C. parapsilosis. However, future studies should explore correlations between MFC and both clinical and microbiological outcomes helping clinicians to deliver a more tailored approach to the treatment of invasive resistant fungal infections.
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